The multifunctional actions of beta-thujaplicin on the oxidative energy transformations as a consequence of its lipophilic and chelating properties.
The influence of the fungicidic compound beta-thujaplicin (beta-isopropyl-tropolone) on the energy transformation processes of oxidative phosphorylation was investigated in isolated rat liver mitochondria with succinate (plus rotenone) as substrate. To elucidate the observed strong inhibition of active respiration by beta-thujaplicin three possibilities were assayed: the inhibition of 1) transport processes across the inner mitochondrial membrane for inorganic phosphate, adenine nucleotides, or succinate, 2) electron flux along the respiratory chain, and 3) mitochondrial ATPase. In this respect a remarkable inhibition of both Pi transport and the translocation of adenine nucleotides could not be observed. However, the effective suppression of the DNP-induced ATPase by beta-thujaplicin explains the pronounced inhibition of active respiration. An impairment of succinate transport and the measured partial inhibition of the terminal respiratory chain at the level of cytochrome oxidase contribute to the less marked inhibition of the uncoupled respiration. The ability of beta-thujaplicin to extract mitochondrial Mg++ and the prevention of the effects of beta-thujaplicin by an excess of Mg++ in the medium suggest a common mode of action of beta-thujaplicin as a lipophilic chelator of Mg++ and other divalent cations.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D003508:Cycloheptanes / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008634:Mersalyl / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D039821:Monoterpenes; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D014334:Tropolone / Q000031:analogs & derivatives / Q000494:pharmacology*
D003508:Cycloheptanes; D004140:Dinitrophenols; D007502:Iron Chelating Agents; D039821:Monoterpenes; D012402:Rotenone; D008634:Mersalyl; D000244:Adenosine Diphosphate; D014334:Tropolone; D004492:Edetic Acid; D008274:Magnesium; C009479:beta-thujaplicin